Differential effects of maturation on nicotinic- and muscarinic receptor-induced ion secretion in guinea pig distal colon

The incidence of constipation increases with age. This has been linked to age-related changes in the structure and function of myenteric neurons regulating intestinal motility; however, the role of submucous neurons is unknown. The aim of this study was to determine the effect of maturation on cholinergic receptor-induced ion secretion in guinea pig colon. Changes in the short-circuit current (Isc) and tissue conductance were monitored in muscle-stripped colonic segments from young (3-4-month-old) and mature (12-15-month-old) male guinea pigs. Thirty-one percent of colonic segments from young guinea pigs exhibited ongoing neural activity, which was absent in mature animals. Baseline Isc was significantly higher only in young guinea pig tissues with ongoing activity. Tissue conductance was similar in all tissues. Electrical field stimulation caused a biphasic increase in the Isc. At 15 V/10 Hz, only Peak 1 was attenuated, whereas both peaks were reduced in mature guinea pigs at 10 V/5Hz. 1,1, dimethyl-4-phenyl-piperazinium(DMPP)-induced ion secretion was blunted in mature guinea pigs. Atropine reduced the 1,1, dimethyl-4-phenyl-piperazinium response only in young guinea pigs. Carbachol-induced ion secretion was similar in tissues from both age groups. In conclusion, nicotinic receptor-induced secretion mediated by both cholinergic and noncholinergic secretomotor neurons was blunted; however, epithelial muscarinic receptor activity was unaltered during maturation.     

Ventricular fibrillation in hibernators and nonhibernators

Previous studies have shown that there are differences between hibernators and nonhibernators in the susceptibility to ventricular fibrillation. In an attempt to clarify these differences ventricular fibrillation was induced in isolated hearts of the hibernator, the woodchuck, Marmota monax by cooling, warming, puncture, and by norepinephrine administration. It was shown that the hearts of the winter animals were completely resistant toward the ventricular fibrillation inducing agents, which was not the case for the hearts from summer, active animals. Further, the hearts of another hibernator, the hedgehog, Erinaceus europaeus, and guinea pig, Cavia porcellus, were studied electrophysiologically in anesthetized animals with open chests and with bipolar electrodes attached to the epicardium. During pacing it was shown that the hedgehog had a higher stimulus threshold and a lower maximal following frequency than the guinea pig. The summer hedgehogs showed resistance toward both ventricular premature beats and ventricular fibrillation. Sixty percent of the summer hedgehogs and 100 percent of the winter hedgehogs and guinea pigs developed ventricular fibrillation. The threshold for ventricular fibrillation was highest for summer hedgehogs. The effective refractory period of papillary muscle of summer hedgehogs was shorter than that of guinea pigs. The force frequency relationship of the isolated papillary muscle showed a greater degree of independence in the hedgehog than in the guinea pig. Consequently, the results show that the heart of the hibernator is more arrhythmia resistant than the heart of the nonhibernator, although there are seasonal differences.     

Effects of hyperoxia and allergic airway inflammation on cough reflex intensity in guinea pigs

Toxic influence of high oxygen concentration on pulmonary function and structures has been known for many years. However, the influence of high oxygen concentration breathing on defensive respiratory reflexes is still not clear. In our previous experiments, we found an inhibitory effect of 100 % oxygen breathing on cough reflex intensity in healthy guinea pigs. The present study was designed to detect the effects of hyperoxia on cough reflex in guinea pigs with allergic airway inflammation. In the first phase of our experiment, the animals were sensitized with ovalbumin. Thirty-two sensitized animals were used in two separate experiments according to oxygen concentration breathing: 100 % or 50 % oxygen for 60 h continuously. In each experiment, one group of animals was exposed to hyperoxia, another to ambient air. The cough reflex was induced both by aerosol of citric acid before sensitization, then in sensitized animals at 24 h and 60 h of exposition to oxygen/air in awake animals, and by mechanical stimulation of airway mucosa in anesthetized animals just after the end of the experiment. In contrast to 50 % oxygen, 100 % oxygen breathing leads to significant decrease in chemically induced cough in guinea pigs with allergic inflammation. No significant changes were present in cough induced by mechanical stimulation of airways.     

Ventricular weights in guinea pigs acclimated to cold plus hypoxia

Weanling male guinea pigs (Cavia porcellus), 2-3 weeks of age, with initial body weights of 207-271 g were exposed for 2-16 weeks to constant cold (6 degrees C) and hypoxia (PO2 = 85 Torr) equivalent to 4800 m above sea level. Their growth rates and body weights did not differ from those of control animals of the same age maintained under normoxic conditions (22 degrees C, PO2 = 133 Torr). After 2, 3, 4, 6, 10, or 16 weeks exposure the animals were sacrificed, the hearts were removed, the ventricles were separated and weighed, and myoglobin concentrations were determined. Total heart weight as well as both right and left ventricular weights increased linearly with age. By the second week of exposure of the guinea pigs to cold plus hypoxia the total heart and right ventricular weights were 25 and 50% greater than those of the normoxic control animals. Both weights increased at greater rates than those of the controls until Week 6 and then remained at 30 and 80% throughout the 16th week. The weights of the left ventricles in these animals were only slightly greater than those of the controls. In spite of the severe right ventricular hypertrophy these animals showed no clinical signs of right heart failure. Myoglobin concentrations were significantly greater in both ventricles for the cold-plus-hypoxic animals than for the controls.     

Improved ECG detection of presence and severity of right ventricular pressure load validated with cardiac magnetic resonance imaging

The study aimed to assess whether the 12-lead ECG-derived ventricular gradient, a vectorial representation of ventricular action potential duration heterogeneity directed toward the area of shortest action potential duration, can improve ECG diagnosis of chronic right ventricular (RV) pressure load. ECGs from 72 pulmonary arterial hypertension patients recorded <30 days before onset of therapy were compared with ECGs from matched healthy control subjects (n = 144). Conventional ECG criteria for increased RV pressure load were compared with the ventricular gradient. In 38 patients a cardiac magnetic resonance (CMR) study had been performed within 24 h of the ECG. By multivariable analysis, combined use of conventional ECG parameters (rsr' or rsR' in V1, R/S > 1 with R > 0.5 mV in V1, and QRS axis >90 degrees ) had a sensitivity of 89% and a specificity of 93% for presence of chronic RV pressure load. However, the ventricular gradient not only had a higher diagnostic accuracy for chronic RV pressure load by receiver operating characteristic analysis [areas under the curve (AUC) = 0.993, SE 0.004 vs. AUC = 0.945, SE 0.021, P < 0.05], but also discriminated between mild-to-moderate and severe RV pressure load. CMR identified an inverse relation between the ventricular gradient and RV mass, and a trend toward a similar relation with RV volume. In conclusion, chronically increased RV pressure load is electrocardiographically reflected by an altered ventricular gradient associated with RV remodeling-related changes in ventricular action potential duration heterogeneity. The use of the ventricular gradient allows ECG detection of even mildly increased RV pressure load.     

Tachykinins mediate bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs

We tested the hypothesis that tachykinins mediate hyperpnea-induced bronchoconstriction (HIB) in 28 guinea pigs. Stimulus-response curves to increasing minute ventilation with dry gas were generated in animals depleted of tachykinins by capsaicin pretreatment and in animals pretreated with phosphoramidon, a neutral metalloendopeptidase inhibitor. Sixteen anesthetized guinea pigs received capsaicin (50 mg/kg sc) after aminophylline (10 mg/kg ip) and terbutaline (0.1 mg/kg sc). An additional 12 animals received saline (1 ml sc) instead of capsaicin. One week later, all animals were anesthetized, given propranolol (1 mg/kg iv), and mechanically ventilated (6 ml/kg, 60 breaths/min, 50% O2 in air fully water saturated). Phosphoramidon (0.5 mg iv) was administered to five of the noncapsaicin-treated guinea pigs. Eucapnic dry gas (95% O2-5% CO2) hyperpnea "challenges" were performed by increasing the tidal volume (2-6 ml) and frequency (150 breaths/min) for 5 min. Capsaicin-pretreated animals showed marked attenuation in HIB, with a rightward shift of the stimulus-response curve compared with controls; the estimated tidal volume required to elicit a twofold increase in respiratory system resistance (ES200) was 5.0 ml for capsaicin-pretreated animals vs. 3.7 ml for controls (P less than 0.03). Phosphoramidon-treated animals were more reactive to dry gas hyperpnea compared with control (ES200 = 2.6 ml; P less than 0.0001). Methacholine dose-response curves (10(-11) to 10(-7) mol iv) obtained at the conclusion of the experiments were similar among capsaicin, phosphoramidon, and control groups. These findings implicate tachykinin release as an important mechanism of HIB in guinea pigs.     

The daily pattern of heart rate, body temperature, locomotor activity, and autonomic nervous activity in congenitally bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs.

We studied the characteristics of the rhythmicity of heart rate (HR), body temperature (BT), locomotor activity (LA) and autonomic nervous activity in bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs. For this purpose, HR, BT, LA, and electrocardiogram (ECG) were recorded from conscious and unrestrained guinea pigs using a telemetry system. Autonomic nervous activity was analyzed by power spectral analysis of heart rate variability. Nocturnal patterns, in which the values in the dark phase (20:00-06:00) were higher than those in the light phase (06:00-20:00), were observed in HR, BT and LA in both strains of guinea pigs. The autonomic nervous activity in BHS guinea pigs showed a daily pattern, although BHR guinea pigs did not show such a rhythmicity. The high frequency (HF) power in BHS guinea pigs was higher than that in BHR guinea pigs throughout the day. Moreover, the low frequency/high frequency (LF/HF) ratio in BHS guinea pigs was lower than that in BHR guinea pigs throughout the day. These results suggest that parasympathetic nervous activity may be predominant in BHS guinea pigs.     

Evaluation of enzyme-linked immunosorbent assay for serodiagnosis of Bordetella bronchiseptica infection in guinea pigs]

An enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of Bordetella bronchiseptica (B. bronchiseptica) infection in guinea pigs was evaluated. An isolate of B. bronchiseptica from lung lesion of a guinea pig was used as antigen after ultrasonication. In the experimental infection, specific pathogen-free guinea pigs inoculated with the bacterium intranasally were examined every 5 or 10 days. The organism was recovered from all animals between 5 and 30 days post-inoculation (p.i.). Only one animal was sero-positive by agglutination test 30 and 50 days p.i.; whereas, by ELISA, one animal was positive 5 days p.i., and all the animals showed strong reaction 20 to 50 (end of experiment) days p.i. Field samples obtained from 1983 to 1989 were tested by ELISA. The results corresponded to those of macroscopic observations and bacterial isolation. The ELISA proved to be useful method for detection of B. bronchiseptica infection in guinea pigs.     

Repeated antigen challenge induced airway hyperresponsiveness to neurokinin A and vagal non-adrenergic, non-cholinergic (NANC) stimulation in guinea pigs.

The effect of repeated weekly antigen challenges by aerosol on bronchopulmonary responses to ACh, histamine, neurokinin A or atropine-resistant (NANC) component of vagal stimulation, has been studied in guinea pigs. Bronchospastic responses were measured in anaesthetized animals, 7 days after the last challenge with antigen (or vehicle). No difference was observed between control and antigen challenged guinea pigs in their responsiveness to acetylcholine (1-300 mumol kg-1 i.v.) or histamine (1-300 mumol kg-1 i.v.). On the other hand, amplitude of bronchospasm induced by neurokinin A (1-3 mumol kg-1 i.v.) or NANC vagal stimulation (20 Hz, 1 msec, 10 V, trains of 5-20 sec) was significantly increased in guinea pigs previously challenged with antigen, as compared to controls. These results suggest that repetitive antigen exposure in sensitized guinea pigs generates an increase in the responsiveness to exogenously administered or endogenously released tachykinins, at a time when no generalized hyperresponsiveness to other spasmogens could be observed.     

ST segment elevation on electrocardiogram: the electrocardiographic pattern of Brugada syndrome

A 77-year-old white diabetic woman was brought to our emergency department (ED) after becoming lightheaded and hypotensive at home. Her routine tests including a chest radiograph were normal. Her electrocardiogram (ECG) showed significant ST segment elevation in leads V1 to V4. Serial cardiac enzymes and troponin were within normal limits. Her ECG met the criteria for type 1 Brugada syndrome. Brugada syndrome, which is more common in young Asian males, is an arrhythmogenic disease caused in part by mutations in the cardiac sodium channel gene SCN5A. To diagnose the Brugada syndrome, 1 ECG criterion and 1 clinical criterion should exist. Brugada syndrome can be associated with ventricular tachycardia or fibrillation; the only treatment proven to prevent sudden death is placement of an implantable cardioverter defibrillator, which is recommended in symptomatic patients or in those with ventricular tachycardia induced during electrophysiologic studies and a type 1 ECG pattern of Brugada syndrome. It is important to recognize the Brugada ECG pattern and to differentiate it from other etiologies of ST segment elevation on ECG.     

Comparison of the effects of estradiol-17beta and the synthetic estrogen, RU-2858, on lordosis behavior in adult female rats and guinea pigs

Female sexual behavior (as assessed by lordosis responses) in adult ovariectomized guinea pigs and rats was measured after a single subcutaneous injection of either the synthetic estrogen RU-2858 or estradiol-17β (E) and a subsequent injection of progesterone (P). Thresholds for responsiveness to each estrogen were determined over a range of doses from 1 to 640 μg/kg of body weight. RU-2858 was able to stimulate lordosis at doses several times lower than E in both guinea pigs and rats. In general, guinea pigs were less sensitive to both estrogenic compounds than rats and were particularly insensitive to E. Approximately 40% of guinea pigs given RU-2858 displayed lordosis prior to P injection. Subsequent P injection did not greatly enhance the intensity of lordosis responses in these animals. These guinea pigs were also more sensitive than the remaining 60% of RU-2858-injected guinea pigs on several indexes of lordosis intensity (e.g., lordosis threshold, duration of heat, duration of individual lordosis responses). Rats did not respond behaviorally to RU-2858 without a subsequent P injection nearly as frequently as did guinea pigs. At the doses used in this study, E did not facilitate lordosis behavior in rats or guinea pigs in the absence of a subsequent P injection.     

Identification of Amino Acids in HA and PB2 Critical for the Transmission of H5N1 Avian Influenza Viruses in a Mammalian Host

Since 2003, H5N1 influenza viruses have caused over 400 known cases of human infection with a mortality rate greater than 60%. Most of these cases resulted from direct contact with virus-contaminated poultry or poultry products. Although only limited human-to-human transmission has been reported to date, it is feared that efficient human-to-human transmission of H5N1 viruses has the potential to cause a pandemic of disastrous proportions. The genetic basis for H5N1 viral transmission among humans is largely unknown. In this study, we used guinea pigs as a mammalian model to study the transmission of six different H5N1 avian influenza viruses. We found that two viruses, A/duck/Guangxi/35/2001 (DKGX/35) and A/bar-headed goose/Qinghai/3/2005(BHGQH/05), were transmitted from inoculated animals to naïve contact animals. Our mutagenesis analysis revealed that the amino acid asparagine (Asn) at position 701 in the PB2 protein was a prerequisite for DKGX/35 transmission in guinea pigs. In addition, an amino acid change in the hemagglutinin (HA) protein (Thr160Ala), resulting in the loss of glycosylation at 158–160, was responsible for HA binding to sialylated glycans and was critical for H5N1 virus transmission in guinea pigs. These amino acids changes in PB2 and HA could serve as important molecular markers for assessing the pandemic potential of H5N1 field isolates.     

Synergistic effects of active specific immunotherapy and chemotherapy in guinea pigs with disseminated cancer

Sewall Wright strain 2 guinea pigs bearing pulmonary metastases of the syngeneic line 10 (L10) hepatocarcinoma were treated with a vaccine composed of 10(7) bacillus Calmette-Guérin admixed with 10(7) x-irradiated L10 tumor cells beginning 10 days after tumor inoculation. Although this treatment failed to cure most of the guinea pigs of their metastatic disease, histologic examination of the pulmonary tumors in the vaccinated guinea pigs provided evidence of a cell-mediated hypersensitivity response that disrupted the normally compact architecture seen in control tumors. When a monoclonal antibody against the L10 tumor was injected i.v. to evaluate the vascular permeability of the tumors, significantly more antibody localized in tumors of vaccinated guinea pigs than in tumors of untreated controls. These results suggested that blood-borne substances could be delivered more efficiently to L10 metastases after the tumor-bearing guinea pigs had been treated with vaccine. To determine whether such increased vascular permeability would enhance the antitumor effects of chemotherapeutic agents, combined immunotherapy and chemotherapy studies were performed. Although cyclophosphamide treatment by itself did not cure L10-bearing guinea pigs, cyclophosphamide used in conjunction with prior immunotherapy increased the survival rate of animals to more than twice that of animals treated with immunotherapy alone (74 vs 33%). These results suggest that one mechanism by which active specific immunotherapy enhances chemotherapy of disseminated tumors is by rendering tumor foci more permeable to subsequently administered cytotoxic drugs.     

New data on the factors of ovarian competence in the immature and mature guinea pigs

The effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on ovulation and luteinization in premature and in mature female guinea pigs in different states of the estrous cycle were compared histologically. FSH and LH were administered in a horse pituitary extract (gonadormone, Byla) injected sc, and results were assessed from hematoxylin and eosin-stained serial sections of the ovaries, removed 24 hours later. In premature guinea pigs (mean weight 233 gm) the threshold dose of gonadormone was .1-1 U for luteinization, and results from different seasons did not differ, so experiments were pooled. At .5 U, 17 of 32 (53%) animals had luteinized follicles, compared to 44 of 56 (79%) given 1 U (p.02). Of these luteinized follicles 2 of 17 (12%) animals had ovulated, or .25 (coefficient of ovulation) of luteinized follicles at .1 U, while 10 of 44 (23%) animals ovulated, or .61 of luteinized follicles ovulated at 1 U. 35 or 70 mg atropine S04 per 100 gm body weight did not affect luteinization induced by 1 U gonadormone. In mature guinea pigs (mean weight 415 gm), 2 of 5 U gonadormone at the beginning of vaginal closure caused luteinization, usually with eggs enclosed (pseudopregnancy), or atresia, in more than 1/2 of the animals. On Day 8 after vaginal closure, 7 of 9 (78%) animals had corpora lutea with enclosed eggs, after receiving 1 U gonadormone. On Day 12, 18 of 51 (35%) animals had corpora lutea with enclosed eggs, 12 of 51 (24%) had postovulatory corpora lutea, and 9 of 51 (18%) had both. Atropine S04 again had no effect on luteinization. If the young guinea pigs given .1 U and the mature guinea pigs given 1 U were compared, the frequency of luteinization was 53% and 76%, respectively (p.05); the frequency of ovulation among animals with luteinization was 12% and 23%, respectively (p.01); and the coefficient of ovulation among luteinized follicles was .25 and .78, respectively (p.05). Therefore, degrees of competence can be assigned since mature follicles at the end of the cycle were more responsive than follicles from premature guinea pigs, whose follicles in turn were more responsive than early follicles of mature guinea pigs.     

Experimental cryptococcosis in guinea pigs

A guinea pig model was used to evaluate immune response to Cryptococcus neoformans. This model shared characteristics with cryptococcosis in humans. Twenty five guinea pigs injected intraperitoneally with 10(7) viable C. neoformans cells developed disseminated disease. Forty days after infection all guinea pigs were killed and autopsy performed. C. neoformans growth in the lungs, brains, livers and spleen of the infected animals were determined. Furthermore, the immune response was characterized by moderate degree of delayed-type hypersensitivity and humoral response. In some organs was observed neutrophil and lymphocyte infiltration with presence of cryptococci cells. The infiltration observed in the organs was probably a consequence of an immune reaction.     

Modeling of pemphigus vulgaris in guinea pigs]

In 146 guinea pigs with body weight of 150-200 g pemphigus vulgaris (PV) was induced using screening techniques. The animals were injected with PV patients' IgG (IgGPV) and blister fluid (PVBF) with the PV patient mononuclears. Intraperitoneal administration of IgGPV caused dystrophy in epidermis of experimental animals while intracutaneous injection of PVBF resulted in balloon dystrophy. Clinical manifestations of -PV were obtained after two-day intraperitoneal IgGPV administration in a total dose of 1.5 g (6 mg/g) following a cycle of intracutaneous injections of 2.0 ml PVBF in 10-15 sites of guinea pig back. The presence of acantholysis, intraepidermal localization of blisters, pemphigus antibodies fixation on spinous cell surface, and almost 100% mortality of experimental animals were the major criteria for the developed model of PV in guinea pigs. Experimental PV in guinea pigs was abolished due to treatment of PVBF with dexamethasone, contrykal, heating (56 degrees C, 30 min), preincubation with human skin samples, and PVBF cell-free supernatant application. The conclusion was made that for occurrence of pemphigus in laboratory animals a combined effect of pemphigus antibodies, sensitized mononuclears, complement and endogenous proteinases is required.     

Congenital malformation of the skeleton in Weiser-Maples guinea pigs]

Some abnormalities were observed in the occipital bone, cervical vertebrae and thoracic vertebrae of Weiser-Maples guinea pigs. In the occipital bone, the medial basilar impression was suggested to occur in 40 (32.8%) out of 122 animals. The basilar impression was classified into right, left and both side types and observed in 24, 11 and 5 animals, respectively. The basilar impression was known to be accompanied in human with some anomalies such as platybasia, Klippel-Feil syndrome, deformation of foramen magnum and so-on. These anomalies were also observed in guinea pigs. The fusion of the axis with the 3rd cervical vertebra was observed in 12 (10.5%) out of 114 animals. The deformation was sometimes observed in the temporal, interparietal, atlas and axis as well as the occipital bone. The fusion of the 7th cervical vertebra with the 1st thoracic vertebra was found in 46 (51.7%) out of 89 animals. This fusion was thought to have no relation with the basilar impression. Weiser-Maples guinea pigs are now in 19 generations of sibmating. Because these abnormalities as mentioned above are all thought to be inherited, the selective breeding will make Weiser-Maples guinea pigs suitable for the study of the basilar impression.     

Effect of immunosuppression on experimental Argentine hemorrhagic fever in guinea pigs.

Immunosuppression with cyclosporin A or cyclophosphamide had no apparent effect on the disease course of guinea pigs infected with a virulent strain of Junin virus. Immunosuppression of guinea pigs infected with an attenuated strain of Junin virus led to fulminating Argentine hemorrhagic fever. All immunosuppressed infected animals died. Virus distribution patterns in target organs, as determined by plaque assay and fluorescent antibody procedures, were similar to those from non-immunosuppressed animals infected with a virulent strain. Histopathological lesions in immunosuppressed guinea pigs infected with an attenuated strain of virus were similar to those in non-immunosuppressed guinea pigs infected with a virulent strain. Histological changes attributable to the immunosuppressive drug(s) were regularly observed. Immunosuppressed animals infected with attenuated Junin virus and non-immunosuppressed animals infected with virulent virus failed to develop antibody or responded at a minimal level. Virus-specific cytotoxic spleen cell activity, previously shown to be antibody dependent, failed to develop in the same animals. The presence of a competent immune response, probably serum antibody, determined whether Argentine hemorrhagic fever infection of the guinea pig was lethal or whether recovery ensued; no evidence for harmful effects of the immune response was obtained.     

Hairless pigmented guinea pigs: a new model for the study of mammalian pigmentation

A stock of hairless pigmented guinea pigs was developed to facilitate studies of mammalian pigmentation. This stock combines the convenience of a hairless animal with a pigmentary system that is similar to human skin. In both human and guinea pig skin, active melanocytes are located in the basal layer of the interfollicular epidermis. Hairless albino guinea pigs on an outbred Hartley background (CrI:IAF/HA(hr/hr)BR; designated hr/hr) were mated with red-haired guinea pigs (designated Hr/Hr). Red-haired heterozygotes from the F1 generation (Hr/hr) were then mated with each other or with hairless albino guinea pigs. The F2 generation included hairless pigmented guinea pigs that retained their interfollicular epidermal melanocytes and whose skin was red-brown in color. Following UV irradiation, there was an increase in cutaneous pigmentation as well as an increase in the number of active epidermal melanocytes. An additional strain of black hairless guinea pigs was developed using black Hr/Hr animals and a similar breeding scheme. These two strains should serve as useful models for studies of the mammalian pigment system.     

Duration and intensity of postvaccinal immunity to plague in experimental animals]

Experiments were conducted on guinea pigs and Papio hamadryas; it was shown that a reduction of the intensity of postvaccinal immunity occurred at various periods after a single vaccination. In inhalation method of immunization in guinea pigs it decreased in 6 months 135 times, in monkeys in one year--133 times. However, at the mentioned periods vaccination provided protection of 50% of the animals from infection with Past. pestis in a dose constitutin 20 to 25 aerosol LD50 for nonimmunized animals. Despite the more pronounced (57--640 times) reduction of the intensity of immunity than in the animals vaccinated by inhalation, in the subcutaneously vaccinated guinea pigs in subcutaneously infected with Past. pestis protection level remained high (resistance index in 3 and 6 months constituted 37.10(6) and 3-3-10(6), respectively).